Bis(bicyclo(2.2.2)octyl)haloboranes

ABSTRACT

A novel class of enolboration reagents represented by the formula 
     
         R.sub.2 BX/R&#39;.sub.3 N 
    
     wherein each R is the same or different alkyl or cycloalkyl, B is boron, X is halo, R&#39; is lower alkyl and / indicates that R 2  BX is preferably employed in the presence of R&#39; 3  N are disclosed. Methods of enolborating a wide variety of organic carbonyl compounds are also provided. Further, new bis(bicyclo[2.2.2.]octyl)haloboranes are efficacious for enolboration.

BACKGROUND OF THE INVENTION

A. Field of Invention

The present invention relates to new reagents which facilitate the enolboration of aldehydes, ketones, carboxylic acids, anhydrides, thioesters, esters and tertiary amides and more particularly relates to novel dialkylhaloboranes.

B. Prior Art

Enolborinates are highly useful intermediates in organic synthesis. See for example: Evans et al., J. Am. Chem. Soc., 979, 101, 6120; Evans et al., Ibid., 1981, 103, 3099; Van Horn et al., Tetrahedron Lett., 1979, 24, 2229; Hirama et al., Ibid., 1979, 24, 2225; Reetz et al., Ibid., 1986, 27, 4721; Hooz et al., J. Am. Chem. Soc., 1968, 90, 5936; Hooz et al., Ibid., 1969, 91, 6195; Mukaiyama et al., Chem. Lett., 1976, 559; Inoue et al., Ibid., 1977, 153; Mukaiyama et al., Ibid., 1979, 559; and Inoue et al., Bull. Chem. Soc. Jpn., 1980, 53, 174. As a result, considerable attention has been paid in the past decade to developing simple methodologies for generating suitable organoboron derivatives, R₂ BX, containing a good leaving group in the presence of a suitable tertiary amine.

The previously .employed reagents include dialkylboron triflates, R₂ BOTf, (Mukaiyama et al., Chem. Lett., 1976, 559; Inoue et al., Ibid., 1977, 153; Mukaiyama et al., Ibid., 1979, 559; and Inone et al., Bull. Chem. Soc. Jpn., 1980, 53, 174); ethylene chloroboronate (Gennari et al., Tetrahedron Lett., 1984, 25, 2279); ROBCl₂ (Chow et al., Helv. Chim. Acta, 1986, 69, 604); BCl₃ (Chow et al., Helv. Chim. Acta, 1986, 69,604); and PhBCl₂ (Hamana et al., Chem. Lett., 1984, 1729. However, these reagents are either difficult to prepare in the pure form or only give moderate conversion to the desired enolborinates.

Further, only one organoboron reagent has been reported to date for the generation of enolborinates from esters. See Corey et al., J. Am. Chem. Soc., 1990, 112, 4976; Corey et al., Tetrahedron Lett., 1990, 31, 3715; Corey et al., Ibid., 1991, 32, 2857; and Corey et al., J. Am. Chem. Soc., 1991, 113, 4026. Essentially no organoboron reagent is now available for the enolization of tertiary amides except for di-n-butylboron triflate, n-Bu₂ BOTf, which has been shown to enolize a special class of reactive tertiary amides, the N, N-dialkyl-2,3,3,3-tetrafluoropropanamides. See Kuoboshi et al., Bull. Chem. Soc. Jap., 1990, 63, 1191; and Joshi et al., J. Am. Chem. Soc. 1988, 110, 6246.

I previously reported the enolboration of two ketones, diethyl ketone and propiophenone with dicyclohexylboron chloride and BCl-9-BBN. Preferential conversion into E enolates was obtained with dicyclohexylboron chloride while primarily Z enolates were obtained with BCl-9-BBN, Chx₂ BOTf and BOTf-9-BBN. See H. C. Brown et al, JACS, 1989, 111, 3441-3442.

We have since discovered a novel class of superior enoboration agents and have additionally discovered that dicyclohexylboron chloride is effective for the selective enolboration of carbonyl compounds other than ketones. These advances in the art were recently described in my articles which appeared as H. C. Brown et al., JOC, 1992, 57, 499-504 and H. C. Brown et al., Ibid., 2716-2721.

The present invention fulfills the need for enolboration agents which exhibit better selectivity and reactivity, are readily accessible and are useful in broader classes of organic compounds.

SUMMARY OF THE DISCLOSURE

The present invention provides a new class of compounds which are useful as reagents for enolboration of ketones and other carbonyl derivatives. The compounds of this invention are represented by the formula:

    R.sub.2 BX

wherein each R is the same or different alkyl or cycloalkyl having from 4 to 10 carbon atoms, B is boron and X is halo with the limitations that R₂ may not be dicyclohexyl when X is chloro and not more than one R may have one carbon atom.

It is preferred to employ the compounds of this invention in the presence of a trialkylamine of the formula R'₃ N wherein and wherein each R' is the same or different lower alkyl having from 1 to 8 carbons. For ease of discussion, the reagents may also be represented by the formula:

    R.sub.2 BX/R'.sub.3 N (or R.sup.1 R.sup.2 BX/R'.sub.3 N)

indicating that the diorganohaloboranes of this invention are employed in the presence of a trialkylamine for best results.

As used herein, "halo" refers to bromo, chloro, fluoro and iodo.

The term "lower alkyl", as used herein, refers to cycloalkyl and straight or branched chain alkyl groups having from 1 to 8 carbon atoms.

The dialkylhaloboranes of this invention are most conveniently prepared by hydroboration of 2 equivalents of a corresponding olefin to R₂ BH with 1 equivalent of boranemethyl sulfide (BMS), followed by addition of the appropriate XH or X₂. Alternatively, the compounds of this invention may be prepared directly from the corresponding olefin by hydroboration with a monohaloborane. The latter method is especially useful in cases where the hydroboration fails to stop cleanly at the dialkylborane stage.

The above methods are shown in the following reactions schemes. ##STR1## wherein R is the desired alkene, for example, cyclohexene.

Since the hydroboration of norbornene and cyclooctene with BMS proceeds rapidly past the desired R₂ BH intermediates to the trialkylboranes, these alkenes are preferably hydroborated with monochloroborane to obtain the desired dialkylchloroboranes.

The novel compounds of the present invention are useful to achieve enolboration of a wide variety of organic compounds including ketones, carboxylic acids, anhydrides, aldehydes, esters and tertiary amides.

The enolization of a broad range of carbonyl compounds by the process of this invention is represented by the following illustrative reaction sequence using dicyclohexylchloroborane in the presence of triethylamine. ##STR2## R=H, alkyl or aryl R'=H, alkyl, aryl, N-dialkyl, N-diaryl, O-alkyl, O-aryl, S-alkyl, or S-aryl

R"=alkyl or cycloalkyl

R'"=alkyl

X=Cl, Br or I

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

In the following examples, all glassware used were thoroughly dried in an oven and cooled and assembled under a stream of nitrogen. Degassed and anhydrous solvents, CCl₄, CH₂ Cl₂, benzene and hexane were used. THF was freshly distilled from sodium benzophenone ketyl. Et₃ N was used after distilling over CaH₂. All alkenes, ketones, aldehydes, carboxylic acids, anhydrides, esters, amides, thioesters and β-keto esters were commercial products of the highest purity available. Whenever necessary, commercially available liquid olefins were purified by distillation over LiAlH₄ and ketones over CaH₂. Borane-methyl sulfide (BMS) and monochloroboranemethyl sulfide (MCBS) reagents were purchased from Aldrich Chemical Company, Inc., Milwaukee, Wis.

¹ H NMR spectra were recorded on T-60-, 200- and 300 MHz instruments. ¹¹ B NMR spectra were recorded on FT-80A and 300-MHz instruments. The chemical shift values are in δ (ppm) relative to BF₃.OEt₂.

EXAMPLE 1 Preparation of Dicyclohexylchloroborane

A 500-mL round-bottom flask capped with a rubber septum, a magnetic stirring bar, and a connecting tube attached to a mercury bubbler was charged with diethyl ether (150 mL) and cyclohexene (41 mL, 400 mmol). The flask was cooled in an ice bath, borane-methyl sulfide (BMS, 20 mL, 200 mmol) was added slowly, and stirring was continued for 3 h at O° C. Dicyclohexylborane precipitated as a white solid. The supernatant liquid was removed by a double-ended needle, the solid was washed with ether, and the liquid was removed. Then the solid was suspended in 100 mL of diethyl ether, and anhydrous HCl in ether (66.7 mL of 3M solution, 200 mmol) was added slowly to the suspension at 0° C. Hydrogen is rapidly evolved and should be safely vented. A clear solution was obtained. The ¹¹ B NMR analysis of the resulting solution showed formation of Chx₂ BCl (δ66 ppm in diethyl ether). Distillation provides the pure title product (δ76 ppm in hexane), 31.6 g, 75% yield, bp 95°-96° C. (0.35 mm).

EXAMPLE 2 Preparation of B-chloro-9-borabicyclo[3.3.1]nonane

The title compound was prepared in 75% yield following the method of Example 1 by treating 9-borabicyclo[ 3.3.1.]nonane (9-BBN, Aldrich Chemical Company, Inc., Milwaukee, Wis.) with anhydrous HCl in ether. ¹¹ B NMR δ79 ppm in hexane, bp 65° C. (0.3 mm).

EXAMPLE 3 Preparation of disiamylchloroborane (Sia₂ BCl)

Following a procedure similar to Example 1, the title compound was prepared in 75% yield from 2-methyl-2-butene. ¹¹ B NMR, δ78 ppm in hexane.

EXAMPLE 4 Preparation of bis(2,5-dimethylcyclohexyl) chloroborane (2,5-Me₂ Chx₂ BCl)

The title compound was prepared in 70% yield by the method of Example 1 from 2,5-dimethylcyclohexene. ¹¹ B NMR, δ74 ppm in ether.

EXAMPLE 5 Alternate Synthesis of Dialkylchloroboranes

The following synthesis of dicyclohexylchloroborane (Chx₂ BCl) is representative of the alternate process of this invention of synthesizing a dialkylchloroborane via hydroboration of an alkene with monochloroborane-methyl sulfide.

A 250-mL round bottom flask fitted with a rubber septum, a magnetic stirring bar, and a connecting tube attached to a mercury bubbler was cooled in an ice bath and charged with diethyl ether (90 mL) under inert atmosphere. Cyclohexene (21.2 mL, 210 mmol) was added, followed by the slow addition of monochloroborane-methyl sulfide (11.6 mL, 100 mmol). The mixture was stirred at 0° C. for 2 h. The solvent was removed under reduced pressure (25° C., 12 Torr). Distillation provided pure dicyclohexylchloroborane (δ76 ppm in hexane), 16.85 g, 80% yield, bp 104°-105° C. (0.5 mm). Synthesis of this product by this process can readily be carried out on a molar scale.

Bis(exo-norbornyl)chloroborane and dicyclooctylchloroborane were prepared using the above procedure.

The following examples illustrate the enolization of various classes of organic compounds using diorganochloroborane in the presence of triethylamine.

EXAMPLE 6 General Procedure for the Enolboration of Ketones

To a stirred solution of dicyclohexylchloroborane (5.2 mmol) and triethylamine (0.73 mL, 5.2 mmol) in carbon tetrachloride (20 mL) cooled at 0° C was added dropwise 2-butanone (5mmol). Enolborinate was generated instantaneously with concurrent formation and precipitation of triethylamine hydrochloride. An internal standard, benzene (0.5 mmol), was added for quantification of the enolborinate by ¹ H NMR analysis. Molarity was adjusted around 0.2-0.3M. The reaction mixture was stirred for the desired length of time and transferred into a centrifuge vial through a double-ended needle (18 gauge). Centrifugation resulted in the separation of the enolborinate solution from Et₃ N.HCl, which was transferred into an NMR tube via, a double-ended needle. ¹ H NMR and ¹¹ B NMR analyses showed the extent of enolization.

EXAMPLES 7-11 Regioselective Enolboration of 2-Butanone with Various R₂ BCl/Et₃ N Reagents

Enolboration of 2-butanone was carried out according to the procedure of example 6 using: (1) B-chloro-9-borabicyclo[3.3.1]nonane (B-Cl-9-BBN); (2) bis(exonorbornyl)chloroborane (exo-Nrb₂ BCl); (3) dicyclooctylchloroborane (Coc₂ BCl); (4) dicyclohexylchloroborane (Chx₂ BCl); (5) diisoamylchloroborane (Sia₂ BCl); and (6) bis (2,5-dimethylcyclohexyl)chloroborane (2,5-Me₂ Chx₂ BCl). Enolizations were carried out in CCl₄ at 0° C. unless otherwise stated using benzene as the internal standard. Both ¹ H NMR (olefinic proton) and ¹¹ B NMR (borinate region) were used to determine the extent of enolization. Examination of the reaction product mixture (olefinic proton) by ¹ H NMR also revealed the regioselectivity of the enolization. The two olefinic protons of the terminal enolate (on the methyl side) appear as two singlets at δ4.2 and 4.4 ppm, and the olefinic proton of the internal enolate (on the ethyl side) appears as a quartet at δ4.7-5.0 ppm. The enolization of 2-butanone is represented by the following reaction scheme: ##STR3## The results are summarized in Table I.

                  TABLE I                                                          ______________________________________                                         Regioselective Enolboration of 2-Butanone with                                 Various R.sub.2 BCl/Et.sub.3 N.sup.a                                                              % regioisomer.sup.c                                         R.sub.2 BCl                                                                           time (min)                                                                               % enolborinate.sup.b                                                                       terminal                                                                               internal                                  ______________________________________                                         1      30        95          67      33                                        2      30        97          99      1                                         3      30        97          99      1                                         4      30        98          99      1                                         5      30        95          99      1                                         .sup. 6.sup.d                                                                         45        92          99      1                                         ______________________________________                                          .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b Determined by .sup.1 H NMR using benzene as an internal standard        and .sup.11 B NMR.                                                             .sup.c Determined by .sup.1 H NMR.                                             .sup.d Reaction at 25° C.                                         

EXAMPLES 12-17 Regioselective Enolboration of 3-Pentanone with Various R₂ BCl/Et₃ N Reagents

After establishing the regioselectivity and reactivity of various R₂ BCl reagents toward an unsymmetrical ketone, 2 -butanone, enolboration of a representative symmetrical ketone, 3-pentanone, was carried out according to the procedure of example 6 using: (1) B-Cl-9-BBN; (2) exoNrb₂ BCl; (3) Coc₂ BCl; (4) Chx₂ BCl; (5) Sia₂ BCl; and (6) 2,5-Me₂ Chx₂ BCl. Reactions were carried out in CCl₄ at 0° C. unless otherwise stated. The results are summarized in Table II.

                  TABLE II                                                         ______________________________________                                         Enolboration of 3-Pentanone with Various                                       R.sub.2 BCl/Et.sub.3 N.sup.a                                                   R.sub.2 BCl time (min)                                                                               % enolborinate.sup.b                                     ______________________________________                                         1           30        95                                                       2           30        96                                                       3           30        97                                                       4           30        96                                                       5           90        32                                                       6.sup.c     45        25                                                       ______________________________________                                          .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b Determined by .sup.1 H NMR using benzene as an internal standard        and .sup.11 B NMR.                                                             .sup.c Reaction at 0° C.                                          

EXAMPLE 18 Representative Enolboration of Aldehydes

A stirred solution of Chx₂ BCl (1.2 mL, 5.5mmol) and Et₃ N (0.77 mL, 5.5 mmol) in CCl₄ (15 mL) was cooled to 0° C. and then phenylacetaldehyde in CCl₄ (5 mL of 1M solution, 5 mmol) was added dropwise over a 20-30 minute period. An immediate precipitate of triethylamine hydrochloride occurred, suggesting a fast reaction. The reaction mixture was stirred at O° C. for 1/2 hr and worked up as described previously for ketones. Analysis by ¹ H NMR and ¹¹ B NMR suggests >95% enolation.

EXAMPLES 19-21

Following the method of Example 18, enolboration of n-butyraldehyde, cyclohexanecarboxaldehyde and isobutyraldehyde were carried out. Table III summarizes the enolboration of simple aldehydes according to the present invention.

                                      TABLE III                                    __________________________________________________________________________     Enolboration of Simple Aldehydes with Chx.sub.2 BCl/Et.sub.3 N.sup.a                     Time              .sup.11 B NMR.sup.b                                                                  .sup.1 H NMR.sup.c                                                                      % enol-                             Aldehyde  (min)                                                                              enolborinate  (δ ppm)                                                                        (δ ppm)                                                                           borinate.sup.d                      __________________________________________________________________________     CH.sub.3 CH.sub.2 CH.sub.2 CHO                                                           30  CH.sub.3 CH.sub.2 CHCH(OBChx.sub.2)                                                          53    4.5-4.78(m)                                                                             95                                                                    and 6.58(d,                                                                    J=6.8 Hz                                     PhCH.sub.2 CHO                                                                           30  PhCHCH(OBChx.sub.2)                                                                          52    5.45(d, J=6.8Hz)                                                                        95                                                                    and 6.70(d, J=                                                                 6.8Hz)                                       (CH.sub.3).sub.2 CHCHO                                                                   45  (CH.sub.3).sub.2 CCH(OBChx.sub.2)                                                            53    6.38(s, 1H)                                                                             94                                   ##STR4## 45                                                                                  ##STR5##     54    6.38(s, 1H)                                                                             94                                  __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C.                 .sup.b .sup.11 B NMR observed as a broad singlet.                              .sup.c Olefinic proton(s).                                                     .sup.d Determined by .sup.1 H and .sup.11 B NMR.                         

EXAMPLE 22 Representative Enolboration of Carboxylic Acids and Derivatives

To a stirred solution of Chx₂ BCl (2.4 mL, 11 mmol, 2.1 equiv) and Et₃ N (1.54 mL, 11 mmol, 2.1 equiv) in CCl₄ (50 mL) cooled to 0° C. was added an internal standard, benzene (0.5 mmol). The molarity of the solution was adjusted to 0.2M with respect to R₂ BCl. Then propionic acid (0.38 mL, 5 mmol, 1 equiv) was added dropwise. An immediate precipitation of Et₃ N.HCl occurred, suggesting a fast reaction. The reaction mixture was stirred at 0° C. for 1 h and worked up as described previously for ketones. Analysis of the olefinic protons by ¹ H NMR suggests >95% enolization of the acid.

EXAMPLE 23-28

Following the method of Example 22, caproic acid, phenylacetic acid, propionic anhydride, S-tert-butyl thioacetate, S-phenyl thioacetate and ethyl acetoacetate were successfully enolized. The results of these representative enolborations is set forth below in Table IV.

                                      TABLE IV                                     __________________________________________________________________________     Enolboration of Carboxylic Acids and Derivatives                               With Chx.sub.2 BCl/Et.sub.3 4N.sup.a                                                      time                .sup.11 B NMR.sup.6                                                                               %                            carbonyl compound                                                                         (min)                                                                              enolborinate    (δ ppm)                                                                        .sup.1 H NMR.sup.c                                                                          enolborinate.sup.d           __________________________________________________________________________     acids.sup.e                                                                    CH.sub.3 CH.sub.2 COOH                                                                    60  CH.sub.3 CH═C(OBChx.sub.2).sub.2                                                           50    4.18 (q, J = 6.8 Hz)                                                                        97                           CH.sub.3 (CH.sub.2).sub.4 COOH                                                            60  CH.sub.3 (CH.sub.2).sub.3 CH═C(OBChx.sub.2).sub.2                                          51    4.10 (t, J = 7.1 Hz)                                                                        95                           PhCH.sub.2 COOH                                                                           60  PhCH═C(OBChx.sub.2).sub.2                                                                  50    5.40 (s)     98                           anhydrides                                                                     (CH.sub.3 CH.sub.2 CO).sub.2 O                                                            60  CH.sub.3 CH═C(OBChx.sub.2)OCOC.sub.2 H.sub.5                                               50    4.9 (q)      90                           acid chlorides.sup.f                                                                          no enolization                                                  esters.sup.f   no enolization                                                  amides.sup.f   no enolization                                                  thioesters.sup.g                                                               CH.sub.3 COSC(CH.sub.3).sub.3                                                             60  CH.sub.2 ═C(OBChx.sub.2)SC(CH.sub.3).sub.3                                                 52    4.85 (s, 1 H), 4.95 (s, 1                                                                   95                           CH.sub.3 COSPh                                                                            30  CH.sub.2 ═C(OBChx.sub.2)SPh                                                                50    4.62 (s, 1 H), 4.73 (s, 1                                                                   90                           β-keto ester                                                              CH.sub.3 COCH.sub.2 CO.sub.2 C.sub.2 H.sub.5                                              60  CH.sub.3 C(OBChx.sub.2)═CHCO.sub.2 C.sub.2 H.sub.5                                         15    4.68 (s, 1 H)                                                                               94                           __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b 11 B NMR observed as broad singlet.                                     .sup.c Olefinic proton(s).                                                     .sup.d Determined by .sup.1 H and .sup.11 B.                                   .sup.e Enolication with 2 equiv. of reagents.                                  .sup.f Enolization at 25° C.                                      

The enolate geometry of enolborinates from representative carbonyl compounds is set forth in Table V below.

                                      TABLE V                                      __________________________________________________________________________     Enolate Geometry of the Enolborinates from Representative Carbonyl             Compounds                                                                                 .sup.1 H NMR.sup. (δ ppm)                                                                     % enolate.sup.b                                carbonyl compound                                                                         syn       anti       Z  E   % yield.sup.c                           __________________________________________________________________________     CH.sub.3 CH.sub.2 COCH.sub.2 CH.sub.3                                                     5.01 (d, J = 4.4 Hz)                                                                     4.72 (d, J = 8.4 Hz)                                                                      21 79  95                                      PhCOCH.sub.2 CH.sub.3                                                                     5.08 (d, J = 4.0 Hz)                                                                     4.88 (d, J = 8.0 Hz)                                                                      <1 >99                                         PhCH.sub.2 CHO.sup.d                                                                        --        --       67 33  95                                      CH.sub.3 CH.sub.2 COOH                                                                    5.17 (d, J = 3.8 Hz)                                                                     4.73 (d, J = 9.1 Hz)                                                                      18 82  95                                      PhCH.sub.2 COOH                                                                             --      5.20 (d, J = 10.0 Hz).sup.e                                                               <1 >99 95                                                   --      3.90 (d, J = 10.0 Hz).sup.f                               (CH.sub.3 CH.sub.2 CO).sub.2 O                                                            5.14 (d, J = 3.9 Hz)                                                                     4.71 (d, J = 8.7 Hz)                                                                      29 71  85                                      __________________________________________________________________________       .sup.a Corresponds to the benzylic proton of the aldol products with          benzaldehyde.                                                                  .sup.b Based on the syn/anti ratio.                                            .sup.c Determined by .sup.1 H NMR analysis (not isolated yield).               .sup.d Directly determined from the enolborinate; see text for .sup.1 H        NMR data.                                                                      .sup.e Corresponds to the benzylic proton α to OH of the aldol.          .sup.f Corresponds to the benzylic proton α to COOH of the aldol.  

Methyl ketones, ethyl ketones, isopropyl ketones, α,β-unsaturated ketones, cyclic ketones, bicyclic ketones, heterocyclic ketones and aromatic ketones have been successfully enolborated according to this invention as well as other carbonyl derivatives including aldehydes, carboxylic acids, anhydrides and thioesters.

The stereoselective enolboration of propiophenone illustrates the exceptional properties of the compounds of this invention. Earlier literature reveals that with prior art reagents and methods, enolboration of propiophenone gave the Z borinate predominately. The highest reported conversion to the E enolborinate was that for the enolboration of propiophenone with R₂ BOTf of only 3%. In the practice of this invention, Propiophenone was converted almost exclusively to the E enolborinate.

As described further below, both aliphatic and aromatic esters and tertiary amides have been enolized employing the reagents and processes of the present invention.

EXAMPLE 29 Preparation of Dicyclohexyliodoborane (Chx₂ BI)

To a suspended solution of dicyclohexylborane (22.3 g, 125.3 mmol) in hexane (100 mL) at 0° C. under a nitrogen atmosphere, solid I₂ (15.95, 62.84 mmol) was added through a side arm in small installments with constant stirring. Hydrogen is evolved and should be safely vented. After adding all the iodine, the reaction mixture is stirred at 0° C. for 2 h and at 25 0° C. for 1 h. A pale pink color persisted which shows the completion of the reaction. The solvent was removed by a water aspirator (20 mm). Distillation of the concentrated mixture under vacuum yielded pure, colorless dicyclohexyliodoborane, bp 198°-200° C. (1.25 mm), 80% yield, ¹¹ B NMR (hexane) δ84 ppm.

EXAMPLE 30 General Method for Enolboration of Esters and Tertiary Amides

To a stirred solution of dicyclohexyliodoborane (1.1 mL), 5.15 mmol) and triethylamine (5.15 mmol) in CCl₄ (15 mL) kept at the required temperature under N₂ atmosphere, the ester or tertiary amide (5.0 mmol) is added dropwise. The enolborinate is generated instantaneously with concurrent formation and precipitation of triethylamine hydroiodide. An internal standard, benzene (0.50 mL, 1.00M in CCl₄, 0.50 mmol) is added (except for the aromatic compounds) for quantification of the enolborinate. The reaction mixture is stirred for 2 h at the same temperature and transferred into a centrifuge vial through a double-ended needle (18 gauge). Centrifugation results in the separation of the enolborinate solution from the solid Et₃ N.HI. In representative cases, this solid was collected and weighed. Essentially quantitative yields are obtained. The enolborinate solution is then transferred into an NMR tube by a double-ended needle. The ¹ H NMR (olefinic proton) analysis gives the extent of enolization and the ¹¹ B NMR spectrum (borinate region, usually broad, 50-56 ppm) confirms the formation of enolborinates. In representative cases, the enolborinates were treated with benzaldehyde and the enolates proved to be highly reactive even at -78° C.

Chx₂ BI is easy to prepare and very stable even at room temperature under an inert atmosphere. No cleavage of ester has been observed. The reaction is essentially instantaneous, even at 0° C. in all cases except for the sterically hindered tert-butyl propionate. Visual observation of the formation of Et₃ N.HI as a pale yellow precipitate as the enolization progresses is an added advantage for this reagent, providing a convenient guide to the course of the reaction. Chx₂ BI thus has proved to be a valuable, practical reagent for the enolization of ester and teriary amides and has achieved for the first time the facile enolization of these organic compounds.

EXAMPLES 31-39

Nine representative esters and tertiary amides were enolborated following the method of Example 30. The results are set forth in Table VI below.

                  TABLE VI                                                         ______________________________________                                         Enolboration of Esters and Tertiary Amides                                     with Chx.sub.2 BI in the Presence of Different Amines.sup.a                    Ester/Amide Amine     .sup.1 H NMR (δ ppm).sup.b                                                             Yield.sup.c, d                             ______________________________________                                         MeCH.sub.2 COOEt                                                                           Et.sub.3 N                                                                               3.97(q, J=7.2Hz)                                                                             96                                                     i-Pr.sub.2 EtN          70                                         PhCH.sub.2 COOEt                                                                           Et.sub.3 N                                                                               4.84(s)       96                                                     i-Pr.sub.2 EtN          95                                         EtCH.sub.2 COOEt                                                                           Et.sub.3 N                                                                               3.96(t, J=7.1Hz)                                                                             95                                         i-PrCH.sub.2 COOEt                                                                         Et.sub.3 N                                                                               3.60(d, f=8.7Hz)                                                                             94                                         t-BuCH.sub.2 COOEt                                                                         Et.sub.3 N                                                                               3.59(s)       84                                         MeCH.sub.2 COOCMe.sub.3                                                                    Et.sub.3 N                                                                               4.11(q, J=6.7Hz)                                                                             60                                                     Et.sub.3 N.sup.e        87                                                     i-Pr.sub.2 EtN          57                                                     i-Pr.sub.2 EtN.sup.e    74                                         MeCH.sub.2 CONMe.sub.2                                                                     Et.sub.3 N                                                                               4.59(q, J=6.7Hz)                                                                             96                                                     i-Pr.sub.2 EtN          86                                         PhCH.sub.2 CONMe.sub.2                                                                     Et.sub.3 N                                                                               4.20(s)       96                                                     i-Pr.sub.2 EtN          93                                         MeCH.sub.2 CONEt.sub.2                                                                     Et.sub.3 N                                                                               3.45(q, J=7.1Hz)                                                                             94                                                     i-Pr.sub.2 EtN          83                                         ______________________________________                                          .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b Corresponds to the olefinic protons of the enolborinates.               .sup.c Based on the .sup.1 H NMR by comparing the integration of the           olefinic proton of the enolborinate with those of the internal standard        benzene (the estimated error limit ±3%).                                    .sup.d In representative cases, the NMR yields were also confirmed by          collecting and weighing the solid Et.sub.3 NHI.                                .sup.e Enolization at 25° C.                                      

The following tables summarize the results of extensive studies of the enolboration of various classes of ketones with dicyclohexylchloroborane in the presence of triethylamine.

                                      TABLE VII                                    __________________________________________________________________________     Enolboration of Methyl Ketones with Chx.sub.2 BCl/Et.sub.3 N.sup.a             RCOR'   time             .sup.11 B NMR.sup.b                                                                  .sup.1 H NMR.sup.c                                                                        % enol-                              R  R'   (min)                                                                              enolborinate (δ ppm)                                                                        (δ ppm)                                                                             borinate.sup.d                       __________________________________________________________________________     Me Me   30  CH.sub.2 ═C(OBChx.sub.2)Me                                                              51    4.18(s, 1H), 4.30(s, 1H)                                                                  100                                  Me Et   30  CH.sub.2 ═C(OBChx.sub.2)Et                                                              51    4.12(s, 1H), 4.25(s, 1H)                                                                  97                                   Me Pr   30  CH.sub.2 ═C(OBChx.sub.2)Pr                                                              52    4.18(s, 1H), 4.28(s, 1H)                                                                  97                                   Me i-Pr 30  CH.sub.2 ═C(OBChx.sub.2)i-Pr                                                            53    4.10(s, 1H), 4.30(s, 1H)                                                                  96                                   Me i-Bu 30  CH.sub.2 ═C(OBChx.sub.2)i-Bu                                                            52    4.20(s, 1H), 4.29(s, 1H)                                                                  95                                   Me neo-pen                                                                             30  CH.sub.2 ═C(OBChx.sub.2)neo-pen                                                         53    4.28(s, 2H)                                                                               95                                   Me Ph   40  CH.sub.2 ═C(OBChx.sub.2)Ph                                                              50    4.55(s, 1H), 5.12(s, 1H)                                                                  95                                   __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b .sup.11 B NMR observed as a broad singlet.                              .sup.c Olefinic proton(s).                                                     .sup.d Determined by .sup.1 H and .sup.11 B NMR.                         

                                      TABLE VIII                                   __________________________________________________________________________     Enolboration of Ethyl Ketones with Chx.sub.2 BCl/Et.sub.3 N.sup.a              RCOR'                                                                               time            .sup.11 B NMR.sup.b                                                                  .sup.1 H NMR.sup.c                                                                        % enol-                                  R R' (h)                                                                               enolborinate (δ ppm)                                                                        (δ ppm)                                                                             borinate.sup.d                           __________________________________________________________________________     Et                                                                               Et 0.5                                                                               CH.sub.3 CH═C(OBChx.sub.2)Et                                                            53    4.65(q, 1H, J=6.3Hz)                                                                      97                                       Et                                                                               i-Pr                                                                              0.5                                                                               CH.sub.3 CH═C(OBChx.sub.2)i-Pr                                                          54    4.67(q, 1H, J=6.5Hz)                                                                      95                                       Et                                                                               i-Bu                                                                              0.5                                                                               CH.sub.3 CH═C(OBChx.sub.2)i-Bu                                                          54    4.64(q, 1H, J=6.3Hz)                                                                      93                                       Et                                                                               t-Bu                                                                              46.sup.a                                                                          CH.sub.3 CH═C(OBChx.sub.2)t-Bu                                                          54    4.65(q, 1H, J=6.4Hz)                                                                      60                                       Et                                                                               Chx                                                                               0.5                                                                               CH.sub.3 CH═C(OBChx.sub.2)Chx                                                           54    4.60(q, 1H, J=6.6Hz)                                                                      94                                       Et                                                                               Ph 1.0                                                                               CH.sub.3 CH═C(OBChx.sub.2)Ph                                                            52    5.10(q, 1H, J=7.4Hz).sup.f                                                                90                                       __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b .sup.11 B NMR observed as a broad singlet.                              .sup.c Olefinic proton(s).                                                     .sup.d Determined by .sup.1 H and .sup.11 B NMR.                               .sup.e Enolization at 25° C.                                            .sup.f Corresponds to [E]-enolate; its [Z]-enolate, obtained after             isomerization, appeared at δ 5.5 ppm (q, J=7.4Hz).                 

                  TABLE IX                                                         ______________________________________                                         Enolboration of Sterically Hindered Ketones with                               Chx.sub.2 BCl/Et.sub.3 N.sup.a                                                 ketone            time (h) % enolborinate.sup.b                                ______________________________________                                         Me.sub.2 CHCOCHMe.sub.2                                                                          1.0      <1                                                  Me.sub.2 CHCOCHMe.sub.2                                                                          24.sup.c 10                                                  Me.sub.2 CHCOPh   1.0      <1                                                  Me.sub.2 CHCOCpn  1.0      <1                                                  2,5-dimethylcyclopentanone                                                                       1.0      <1                                                  2,6-dimethylcyclohexanone                                                                        1.0      <1                                                  ______________________________________                                          .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b Determined directly by .sup.11 B NMR of the enolborinate and            indirectly by .sup.1 H NMR of its benzaldehyde aldol product.                  .sup.c Enolization at 25° C.                                      

                                      TABLE X                                      __________________________________________________________________________     Enolboration of α, β-Ketones with Chx.sub.2 BCl/Et.sub.3            N.sup.a                                                                                 time         .sup.11 B NMR.sup.b                                                                  .sup.1 H NMR.sup.c                                                                       % enol-                                  ketone   (min)                                                                              enolborinate                                                                            (δ ppm)                                                                        (δ ppm)                                                                            borinate.sup.d                           __________________________________________________________________________      ##STR6##                                                                               60                                                                                  ##STR7##                                                                               52    5.1(t, 1H)                                                                               85                                        ##STR8##                                                                               60                                                                                  ##STR9##                                                                               53    4.4(s, 1H), 4.5(s, 1H)                                                                   65                                        ##STR10##                                                                              30                                                                                  ##STR11##                                                                              51    4.9(s, 1H), 5.0(s, 1H)                                                                   90                                       __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b .sup.11 B NMR observed as a broad singlet.                              .sup.c Olefinic proton(s) of the enolate double bond.                          .sup.d Determined by .sup.1 H and .sup.11 B NMR.                         

                                      TABLE XI                                     __________________________________________________________________________     Enolboration of Cyclic Ketones with Chx.sub.2 BCl/Et.sub.3 N.sup.a                     time        .sup.11 B NMR.sup.b                                                                  .sup.1 H NMR.sup.c                                                                      % enol-                                     ketone  (min)                                                                              enolborinate                                                                           (δ ppm)                                                                        (δ ppm)                                                                           borinate.sup.d                              __________________________________________________________________________      ##STR12##                                                                             35.sup.e                                                                            ##STR13##                                                                             53    4.80(s, br)                                                                             98                                           ##STR14##                                                                             45                                                                                  ##STR15##                                                                             53    4.92(t, br)                                                                             98                                           ##STR16##                                                                             30                                                                                  ##STR17##                                                                             54    4.95(t, J=5.8Hz)                                                                        96                                           ##STR18##                                                                             30                                                                                  ##STR19##                                                                             54    4.85(t, J=5.8Hz)                                                                        96                                           ##STR20##                                                                             45                                                                                  ##STR21##                                                                             52    4.87(t, br)                                                                             95                                           ##STR22##                                                                             45                                                                                  ##STR23##                                                                             50    4.80(t, br)                                                                             95                                          __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b .sup.11 B NMR observed as a broad singlet.                              .sup.c Olefinic proton(s).                                                     .sup.d Determined by .sup.1 H and .sup.11 B NMR.                               .sup.e Enolization at 25° C.                                      

                                      TABLE XII                                    __________________________________________________________________________     Enolboration of Bicyclic and Heterocyclic Ketones                              with Chx.sub.2 BCl/Et.sub.3 N.sup.a                                                       time                   .sup.11 B NMR.sup.b                                                                  .sup.1 H NMR.sup.c                                                                       % enol-                      ketone     (min)                                                                              enolborinate       (δ ppm)                                                                        (δ ppm)                                                                            borinate.sup.d               __________________________________________________________________________      ##STR24## 30.sup.e                                                                            ##STR25##         53    4.85(d, J=3.4Hz)                                                                         96                            ##STR26## 30.sup.e                                                                            ##STR27##         53    4.82(d, J=3.4 Hz)                                                                        92                            ##STR28## 45                                                                                  ##STR29##         52    5.22(t, J=4.0 Hz)                                                                        95                            ##STR30## 30.sup.f                                                                            ##STR31##         54    I: 5.10(s, br) II: 5.28(s,                                                               90)                           ##STR32## 60.sup.g                                                                            ##STR33##         53    4.95(s, br)                                                                              70                           __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b .sup.11 B NMR observed as a broad singlet.                              .sup.c Olefinic proton(s).                                                     .sup.d Determined by .sup.1 H and .sup.11 B NMR.                               .sup.e Enolization at 25° C.                                            .sup.f Regioisomers I:II = 60:40.                                              .sup.g Enolization without Et.sub.3 N.                                   

                                      TABLE XIII                                   __________________________________________________________________________     Enolboration of Aromatic Ketones with Chx.sub.2 BCl/Et.sub.3 N.sup.a           RCOR'                                                                               time            .sup.11 B NMR.sup.b                                                                  .sup.1 H NMR.sup.c                                                                        % enol-                                  R R' (min)                                                                              enolborinate                                                                               (δ ppm)                                                                        (δ ppm)                                                                             borinate.sup.d                           __________________________________________________________________________     Ph                                                                               Me 40  CH.sub.2 ═C(OBChx.sub.2)Ph                                                             50    4.55(s, 1H), 5.12(s, 1H)                                                                  95                                       Ph                                                                               Et 60  CH.sub.3 CH═C(OBChx.sub.2)Ph                                                           52    5.10(q, J=7.4Hz)                                                                          90                                       Bn                                                                               Me 60  CH.sub.2 ═C(OBChx.sub.2)Bn                                                             52    4.20(s, 1H), 4.40(s, 1H)                                                                  95                                                PhCH═C(OBChx.sub.2)Me                                                                        5.68(s, 1H)                                         Bn                                                                               Et 60  PhCH═C(OBChx.sub.2)Et                                                                  52    5.73(s, 1H), 5.59(s, 1H)                                                                  94                                       Bn                                                                               Ph 60  PhCH═C(OBChx.sub.2 2)Ph                                                                53    6.40(s, 1H), 6.20(s, 1H)                                                                  92                                       Bn                                                                               i-Pr                                                                              60  PhCH═C(OBChx.sub.2)i-Pr                                                                52    5.60(s, 1H)                                                                               90                                       __________________________________________________________________________      .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b .sup.11 B NMR observed as a broad singlet.                              .sup.c Olefinic proton(s).                                                     .sup.d Determined by .sup. 1 H and .sup.11 NMR.                          

                                      TABLE XIV                                    __________________________________________________________________________     Results of Enolate Geometry of the Enolborinates                               Derived From Various Ethyl and Benzyl Ketones using                            Chx.sub.2 BCl/Et.sub.3 N                                                       RCOR" .sup.1 H NMR.sup.a (δ ppm)                                                                 % enolate.sup.b                                        R  R' syn/[Z]  anti/[E] [Z]  [E]  % yield.sup.c                                __________________________________________________________________________     Et Et 5.01(d, J=4.4Hz)                                                                        4.72(d, J=8.4Hz)                                                                        21   79   97                                           Et i-Pr                                                                              4.63(d, J=6.0Hz)                                                                        4.43(d, J=8.6Hz)                                                                        <1   >99  90                                           Et i-Bu                                                                              5.00(d, J=4.5Hz)                                                                        4.71(d, J=8.2Hz)                                                                        12   88   90                                           Et t-Bu                                                                              4.80(d, J=4.0Hz)                                                                        4.68(d, J=8.0Hz)                                                                        <1   >99  56                                           Et Chx                                                                               4.81(d, J=5.0Hz)                                                                        4.63(d, J=8.0Hz)                                                                        <1   >99  90                                           Et Ph 5.08(d, J=4.0Hz)                                                                        4.88(d, J=8.0 Hz))                                                                      <1   >99  87                                           Bn Me 5.68(s, 1H)                                                                             --       >99  <1   91                                           Bn Et 5.73(s, 1H)                                                                             5.59(s, 1H)                                                                             60   40   90                                           Bn Ph 6.40(s, 1H)                                                                             6.20(s, 1H)                                                                             20   80   88                                           Bn i-Pr                                                                              --       5.60(s, 1H)                                                                             <1   >99  87                                           __________________________________________________________________________      .sup.a Corresponds to the benzylic proton of the benzaldehyde aldol            products in the case of ethyl ketones and to the olefinic proton(s) of th      enolborinate in the case of benzyl ketones.                                    .sup.b Based on the syn/anti ratio in the case of ethyl ketones.               .sup.c Determined from the .sup.1 H NMR (not isolated yield).            

EXAMPLE 40 Preparation of bis(bicyclo[2.2.2 ]octyl)chloroborane (Bco₂ BCl)

The title compound was prepared by the method of Example 1 from bicyclo[2.2.2 ]oct-2-ene. The resulting Bco₂ BCl (>98% pure based on ¹¹ B NMR, δ80 ppm in ether) is a colorless liquid and can be used directly since it decomposes on attempted distallation at 0.1 mm.

Upon reaction with ketones, Bco₂ BCl achieves the E enolborinates with a selectivity equal to or higher than that achieved with Chx₂ BCl. Table XV illustrates this observation.

                  TABLE XV                                                         ______________________________________                                         Comparison of Bco.sub.2 BCl/Et.sub.3 N/Et.sub.3 N for the                      Stereoselective Enolboration of Various Ketones                                RCOR'   ChxBCl.sup.b (%) Bco.sub.2 BCl.sup.b (%)                               R    R'     Z       E      yield.sup.c                                                                          Z     E      yield                            ______________________________________                                         Et   i-Pr   <3      >97    95    21 3  >97    94                               Et   Chx    <3      >97    96    <3    >97    95                               Et   t-Bu   <3      >97    60    <3    >97    .sup. 55.sup.d                   Et   Ph     <3      >97    92    <3    >97    90                               Et   Et     21      79     95    3     97     90                               Et   i-Bu   17      83     96    11    89     94                               n-Pr n-Pr   20      80     95    <3    >97    94                               n-Bu n-Bu   29      71     95    <3    >97    93                               ______________________________________                                          .sup.a Reactions were carried out in CCl.sub.4 at 0° C. unless          otherwise stated.                                                              .sup.b Z/E ratio was determined based on the syn/anti ratio of their           corresponding benzaldehyde aldol products.                                     .sup.c Determined by .sup.1 H NMR.                                             .sup.d Reaction at 25° C.                                         

Reference to "alkyl" herein refers to both straight and branched chain alkyl.

From the foregoing, it will be apparent to those skilled in the art that the above examples are illustrative and that modifications may be made without departing from the spirit and scope of the claims. 

I claim:
 1. A di(cycloalkyl)haloborane represented by the formula:

    R.sub.2 BX

wherein each R is bicyclo[2.2.2]octyl and X is halo.
 2. Bis(bicyclo[2.2.2]octyliodoborane.
 3. Bisbicyclo[2.2.2]octylchloroborane. 